The objective of the project is to develop an injectable biodegradable sustained action-L-methadone microcapsule formulation which maintain therapeutic plasma levels for one week following a single administration. The formulation would be a significant improvement over the current methadone maintenance therapy which requires several weekly oral doses of methadone. During Phase I, several batches of microcapsules were prepared and the feasibility of a one week delivery system was established. These microcapsules maintained a sustained plasma level of L-methadone for a period of 7 to 12 days in rats and in rabbits. During Phase II the development of the microcapsules will continue. Improved prototype formulations will be evaluated for in vitro release kinetics, surface morphology, drug content, size distribution, residual solvent and polymer degradation. In vivo release rates and pharmacokinetics will be studied in rabbits. Local tissue irritation will be evaluated. Duration of pharmacological activity will be studied by suppression of withdrawal symptoms of dependent monkeys. To conclude Phase II subchronic toxicology will be evaluated, and manufacturing specifications, processes and controls will be documented in accordance with cGMP regulations. Documentation will be prepared for an IND application, and material will be prepared for initial human tests. The documentation and materials will be supplied to NIDA to conduct clinical trials in Phase III.